Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. FXR is expressed in various organs and shown to be involved in the regulation of many diseases and conditions, such as liver diseases, lung diseases, renal diseases, intestinal diseases, and heart diseases, and biological processes, including glucose metabolism, insulin metabolism, and lipid metabolism.
Numerous bile acid derivatives are FXR agonists, and are able to regulate FXR-mediated diseases and conditions. Obeticholic acid (i.e., OCA, 6-ethylchenodeoxycholic acid, or 6-ECDCA) possesses potent FXR agonistic activity. Various methods of synthesizing OCA have been described, for example, in WO2002/072598, WO2006/122977, and more recently WO2013/192097. However, there are still needs for improved processes that are capable of preparing OCA and derivatives thereof with an increased yield; reduced cost, and good safety profile. The present application addresses such needs.